Interstitial cystitis (IC) is a chronic disease of unknown etiology for which there is no satisfactory therapy. Histopathologically, the common finding in IC is specific epithelial damage (Hunner's ulcers and/or epithelial ruptures with submucosal hemorrhage). Therefore, as putative target cells for an etiologic agent of IC, human bladder transitional epithelial cells (HBTEC) will be grown in monolayers. Urine and bladder tissue of IC patients will be investigated from an etiologic agent(s). For these investigations, we have assembled individuals from the fields of urology, cell biology, immunology, cell monolayer permeability, microbiology, molecular biology, marine biology, and toxicology. The following hypotheses will be tested: 1) That live HBTEC of IC patients and of controls can be grown in cell culture and be used as a resource for the study of IC. Cell and permeability characteristics of HBTEC will be determined. 2) That urine of IC patients contains a non-living substance which damages transitional epithelium. Urine of IC patients and controls will be compared for cytotoxicity to and changes in permeability of HBTEC and the active agent(s) will be isolated by a series of purification techniques. Toxins, antibodies, and cytokines will be specifically sought. 3) That a microorganism on or in transitional epithelium or urine initiates IC by damaging the epithelium. Three specific types of organisms will be sought: a) on or in bladder epithelium but not in urine; b) culturable by only special techniques; and c) viable but non-culturable, thus requiring special visualization processes. A substantially higher prevalence of a candidate organism in IC than in control patients will generate a hypothesis that it is an etiologic agent of IC that can be tested in larger clinical studies. Antibody and CMI response to a candidate organism will be measured in IC and control patients, the organism will be tested in vitro for HBTEC cytotoxicity and permeability, and screening tests suitable for clinical diagnosis will be developed.